Although the structural basis of IP3R activation remains poorly understood, it is clear that the suppressor domain provides an essential link between Ins(1,4,5) P3 binding to the Ins(1,4,5) P3-binding core and opening of the pore [ 11, 12].
Levosimendan has a dual mechanism; it causes Ca2+ sensitization through binding to Troponin C and opening of ATP-dependent K+ channels in vascular smooth muscle.
These regions control the closing and opening of the substrate binding site in GSK-3β(p)·ATP and GSK-3β·ATP, respectively.
Obviously, the described above stepwise binding mechanism, where intrinsic disorder of some proteins allows them to interact with hidden binding sites of ordered partners, represents a special case of a more general allosteric mechanism, where the complex formation between an IDP and its target leads to conformational changes in a target and opening of a hidden binding site.
ATP turnover and trapping with Vi, but not AMP-PNP binding, induces opening of (B ) the extracellular side and (C ) the closing of the intracellular side of the transporter.
These results indicate that residues within the binding pocket play a central role in transforming agonist binding into opening of the P2X receptor channel.
Deletion of G9a in preadipocytes or inhibition of G9a methyltransferase activity increases PPARγ expression and adipogenesis by promoting C/EBPβ binding to and chromatin opening of the PPARγ gene locus [ 81].
The most striking consequence of this rotameric adjustment of the channel to drug binding is the opening of a direct lateral conduit between the internal cavity and the lipid bilayer, a third pathway into the central cavity of the channel.
This region has been proposed to be a signal transduction module, linking the conformational change associated with ATP binding to the opening of the channel pore [ 5, 6].
X-ray crystallography, molecular dynamics calculations, and a variety of functional studies are combined in investigating substrate binding, product binding, and the ring opening mechanism of AHL lactonase.
